The present invention relates to mass spectrometry and, more particularly, to a system and method in which a particle beam is introduced into a mass spectrometer for analysis. A major objective of the present invention is to provide for a stronger signal strength in the mass analyzer output.
GC/LC/MS systems, which combine gas chromatography (GC), liquid chromatography (LC) and mass spectrometry (MS), are used for several purposes including 1) environmental studies, for example, to evaluate water, soil, and waste; 2) food analysis, to identify contaminants and adulterants; 3) pharmaceutical development, to analyze natural and synthetic products; and 4) life sciences, to characterize protein components.
Chromatography includes a class of separation techniques in which, at any given time during separation, some molecules of a component are adsorbed to a stationary solid support, while other molecules are carried by a mobile fluid. The adsorbed molecules are said to be in a "stationary phase" while the fluid-borne molecules are said to be in a "mobile phase".
At equilibrium, the rate at which a component's molecules in the stationary phase are released to the mobile phase equals the rate at which the same component's molecules in the mobile phase are adsorbed to the stationary phase. For each component, the ratio of the number of molecules in the stationary phase to the number of molecules in the mobile phase is quantified by a partitioning coefficient. This partitioning coefficient thus corresponds to the average percentage of time the molecules of a component are in the mobile phase. This percentage correlates with the mobility of the component past the solid support. Sample components with different mobilities separate, as they progress past the solid support. With sufficient separation, the components emerge serially in the chromatography effluent.
Both liquid chromatography and gas chromatography systems are known. In liquid chromatography, the fluid can be an organic liquid solvent, an aqueous liquid solvent, or a mixture of organic and aqueous solvents. In gas chromatography, the fluid can be a carrier gas. The effluent is, of course, liquid in the LC case, and gaseous in the GC case. GC tends to be preferred for volatile components, while LC provides a complementary alternative for nonvolatile components.
To complete the analysis of a sample mixture, the eluting components need to be identified and quantified. Mass spectrometers provide for fast, sensitive, high-resolution identification and quantification. A mass spectrometer provides a mass spectrum of a sample component by filtering sample subcomponents according to molecular mass and quantifying the number of subcomponent molecules at each molecular mass.
A typical mass spectrometer accepts a particle beam input, the particles of the beam being analyte molecules. The mass spectrometer includes an ion source that is activated to ionize the analyte molecule and form an ion beam. The ion beam is then sweep-filtered according to charge-to-mass ratio. The mass spectrometer can include an electron multiplier to detect and quantify the swept ion beam output. The time-varying output of the electron multiplier is a mass spectrum of concentration as a function of charge-to-mass ratio.
The output of a gas chromatography column is a particle-beam of carder gas and gaseous analyte molecules. Generally, the GC particle-beam is compatible with the mass spectrometer, so no specialized GC/MS interface is required. However, when a GC packed column is used, a gas jet separator can be used to remove the bulk of the carrier gas. The GC particle-beam entering the mass spectrometer is ionized and mass analyzed.
The liquid output of the LC system is not directly compatible with the requirements for ionization and the vacuum conditions of the mass spectrometer. Accordingly, LC/MS interfaces can include a particle-beam generator that converts liquid effluent into a particle beam. A typical particle-beam generator comprises a nebulizer gas source, a nebulizer, a desolvation chamber, a momentum separator, and a transfer probe. In the nebulizer, the LC effluent is joined by a stream of helium and converted into an aerosol of uniform droplets. Solvent is vaporized as the droplets traverse the desolvation chamber, freeing sample particles.
The sample particles proceed as a beam through a momentum separator. Vacuum pumps maintain the momentum separator at a lower pressure than the desolvation chamber. The vacuum pumps divert throughgoing particles laterally, drawing lower momentum helium and solvent vapor into the vacuum exhaust system. The higher momentum sample particles remain in a particle beam that enters the mass spectrometer via the transfer probe. This particle beam is then well matched to the mass spectrometer requirements. The sample particles are then ionized and mass analyzed by the mass spectrometer.
GC/LC/MS systems provide for broad sample type compatibility with the advantages of mass spectrometry. To make dual use of mass spectrometer components, the GC and LC inputs to the mass spectrometer can be diametrically opposed. A GC/LC/MS system can be operated in a GC mode, when a GC compatible sample is to be analyzed, and in an LC mode, when an LC compatible sample is to be analyzed. To minimize signal noise, it is standard practice to close the LC input when in GC mode, and to close the GC input when in LC mode.
When sample quantities are small, it is important to keep analyte losses to a minimum in the spectrometer. This is true for GC, but especially true for LC, where losses in the mass spectrometer compound losses in the particle beam generator. Furthermore, LC typically yields large molecules that are subject to fragmentation during ionization. This fragmentation distributes what would have been a single peak into multiple smaller peak, reducing signal-to-noise ratio and complicating interpretation of the mass spectrogram. What is needed is a system and method that minimizes this fragmentation and loss of LC analyte in a mass spectrometer.